Rabies: Still a Uniformly Fatal Disease? Historical Occurrence, Epidemiological Trends, and Paradigm Shifts

Rabies has the highest case fatality of any infectious disease. Pathobiological and clinical insights have questioned the assertion that death is inevitable after onset of acute encephalomyelitis. Relying upon national laboratory-based surveillance, we reviewed records of human rabies acquired in the United States during 1960-2009. Changes in the epidemiology of human rabies were notable, due to improved animal management, safer and more efficacious biologics, and revisions in prevention guidelines. Historically, domestic animals were the most important source of infection. Since the 1990s, more human cases were associated with rabid bats. Prior to 1980, postexposure prophylaxis failures were reported. After development of modern rabies immune globulin and vaccines, none occurred. Of 75 human cases identified, only four patients survived. Rabies remains an extremely high consequence zoonosis, but the disease is not uniformly fatal, per se. Rabies is essentially preventable when primary exposures are averted, or appropriate prophylaxis occurs before illness.     

Epidemiology of dog bites: a community-based study in India

Rabies is a deadly disease with no cure which is mainly caused by dog bites. Data on dog bites and knowledge, attitude and practices (KAP) related to dog bites are not generally available to rural communities. We made a cross-sectional study of a rural community of ten villages served by a primary health centre selected by random sampling. Ten per cent of households selected by systematic random sampling were interviewed for KAP regarding dog bites. The dog bite rate was 25.7/1000 population per year. The rate for males was higher than for females; half of the bites were in summer; 40% did not go for any prophylaxis; half of the victims treated their wounds with chilli powder. Eighty per cent of the bites were class II or III and leg bites were most common. The majority of the community knew dog bites can cause death but they did not know the correct incubation period. Most knew that injections were available to prevent rabies. Only half said they would visit a hospital for treatment. Around 50% received tetanus toxoid.     

Knowledge and practices about rabies among travel medicine consultants in Greece

The number of travellers returning with animal bites from rabies enzootic areas has increased in Greece. The aim of this study was to assess the knowledge of travel-associated risk and preventive measures for rabies. A questionnaire was sent to Travel Medicine consultants in all prefectures. Of 100 Travel Medicine consultants, advice about rabies was given to long-term travellers, business travellers, travellers to rural areas, and travellers engaged in animal activities in rabies enzootic countries by 44%, 22%, 58%, and 75% of them respectively. Avoidance of animals, post-exposure medical assistance, return back to their country, and special caution about children was recommended by 89%, 95%, 8%, and 65% of them, respectively. Rabies pre-exposure vaccination was recommended for travellers to rural areas, long-term travellers, and travellers engaged in animal activities by 61%, 35%, and 81% of them, respectively. Regarding post-exposure vaccination, 78% and 37% answered correctly with regards to travellers with no pre-exposure prophylaxis and travellers with pre-exposure prophylaxis, respectively. Counselling about rabies and management of risk exposure needs to be improved. Our findings indicate the need to promote continuous training in Travel Medicine in Greece and provide practical information about rabies prophylaxis.     

Emerging aspects of rabies infection: with a special emphasis on children

PURPOSE OF REVIEW: Increased awareness of the long-neglected rabies virus could promote the highly effective methods of preventing human deaths. Rabies and rabies-related lyssaviruses have recently been appearing in unexpected places, sometimes with dire consequences. Although rabies of canine origin remains 100% fatal in human beings, should the surprising recovery of a single unvaccinated child influence treatment now? RECENT FINDINGS: Evidence of rabies-related lyssavirus infection of bats is increasing across continents and with new virus types. Human rabies has been misdiagnosed as cerebral malaria, or even drug abuse. Organ transplant recipients have been infected. The first unvaccinated patient, a teenager, bitten by a bat, recovered from rabies encephalitis, but why might this be? Highly effective control and prevention of infection is possible. Preexposure prophylaxis for schoolchildren could now become routine. Improved economical intradermal postexposure vaccine regimens could increase the availability of affordable treatment in developing countries. Controlling dog rabies could prevent 95% of human deaths, but education and resources are lacking. SUMMARY: The risks and problems of rabies and other lyssaviruses vary greatly across the world. Knowledge of epidemiology and prevention could save the lives of victims of animal bites and promote efforts to control and even eliminate dog rabies.     

Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus

Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.     

Post exposure management of animal bite cases attending a primary health center of Delhi

Rabies is an ancient disease of mankind. Every year 4 million people are exposed worldwide after animal bite and around 60000 fell victim to the rabies of which more than 95% of cases are bitten by the dogs. Rabies is a disease associated with many myths. The present study was conducted to find out the clinical profile of the animal bite cases including the common practices, precautions adopted by them after animal bite and lastly the extent and completion of post exposure treatment. Total 147 cases of animal bites attended the OPD during the study. In present study, 123 (83.7%) cases were bitten by dogs, followed by monkey (8.2%) and cat (8.2%). Majority (54.4%) suffered class II bites followed by class I (31.3%) and class III bite (14.3%). Of the total 147 cases, 116 cases (78.9%) completed post exposure prophylaxis which was observed higher among male and in younger age group.     

Cryptogenic rabies, bats, and the question of aerosol transmission

Human rabies is rare in the United States; however, an estimated 40,000 patients receive rabies postexposure prophylaxis each year. Misconceptions about the transmission of rabies are plentiful, particularly regarding bats. Most cases of human rabies caused by bat variants have no definitive history of animal bite. Three hypotheses are proposed and reviewed for the transmission of rabies from bats to human beings. They include nonbite transmission (including aerosol transmission), the alternate host hypothesis (an intermediate animal host that acquires rabies from a bat and then transmits rabies to human beings), and minimized or unrecognized bat bites. Nonbite transmission of rabies is very rare, and aerosol transmission has never been well documented in the natural environment. The known pathogenesis of rabies and available data suggest that all or nearly all cases of human rabies attributable to bats were transmitted by bat bites that were minimized or unrecognized by the patients.     

Fatal case of human rabies infection: A case report

Rationale: Rabies, as an acute viral disease of the mammal's central nervous system(CNS), with a high mortality rate, is transmitted to humans through the bite of a rabid animals, especially canine and feline. Patient concerns: An Afghan man, aged 50 years was bitten by a fox in a farm around the Qom-Tehran road, Central Iran in 2018. The patient visited the doctor after the bite, however the period between incidence and hospital visit was not established and no indication was given whether the bite site injury was thoroughly washed. The patient was neither referred to the health center for vaccination(post-exposure prophylaxis) nor an effective therapeutic measures was applied. Forty-five days post-exposure, the patient presented with symptoms such as headache, fever, tingling and burning sensation and was referred to the Centers for Disease Control and Prevention(CDC) unit of Qom Provincial Health Center. Diagnosis: Rabies infection. Interventions: Forty-five days after the animal bite, in CDC of Qom Health Center, he received rabies post-exposure prophylaxis treatment and was referred to an infectious diseases physician. Based on the history of animal bites, the patient was classified as probable case of rabies. The clinical symptoms of rabies appeared in patient after hospitalization. Outcomes: Ultimately the patient died in hospital 4 days after hospitalization(50 days after the occurrence of animal bite). After referring the patient to the CDC, the patient's saliva(0.5-1 mL) was sampled three times every 3-6 hours and tested by PCR. Human rabies was confirmed by Department of Virology in the Pasteur Institute of Iran. Lessons: Physicians and clinicians have responsibilities to be critical in observations and take prompt actions in case of animal bites, as rabies usually develops within 7 to 14 days, and delayed intervention after the onset of symptoms, vaccine and serum injections cannot lead to the survival of the patient.     

Human Rabies: a 2016 Update

Rabies is a zoonotic disease that is usually transmitted to humans by animal bites. Dogs are the most important vector worldwide. There are encephalitic and paralytic forms of the disease. There are differences in the clinical features of the disease acquired from dogs and bats. Neuroimaging is non-specific. Confirmatory diagnostic laboratory tests for rabies include detection of neutralizing anti-rabies virus antibodies in serum or cerebrospinal fluid and rabies virus antigen or RNA in tissues or fluids. Rabies is preventable after recognized exposures with wound cleansing and administration of rabies vaccine and rabies immune globulin. Rabies is virtually always fatal after clinical disease develops, and there have only been rare survivors. The Milwaukee protocol, which includes therapeutic coma, has been shown to be ineffective and should no longer be used. The development of novel therapeutic approaches may depend on a better understanding of basic mechanisms underlying the disease.     

Rabies in Thailand: 1990

Of the more than 100,000 courses of postexposure rabies treatment given in Thailand annually, 95% consist of brain tissue-derived vaccine without immune globulin. Rabies tissue culture vaccines and immune globulins are expensive by the standards of developing countries. When they are given according to either of two proven intradermal postexposure schedules, significant savings can be achieved without loss of efficacy. Purified equine rabies immune globulins account for approximately 10% of the cost of human products administered to exposed individuals and have been shown to be safe and effective. A canine preexposure immunogenicity study with a potent, inactivated tissue culture vaccine revealed that 12.5% of Thai dogs failed to develop protective antibody titers 2 months after one subcutaneous injection. Previous studies have shown significant antigenic differences between Thai street rabies virus and European and North African strains.     

Assessment of rabies exposure risk among Israeli travelers

BACKGROUND: The decision whether or not to administer rabies pre-exposure prophylaxis (PEP) to travelers visiting endemic areas is a complex one. Paramount for making that decision is knowledge of the risk of animal bites during travel. This study attempts to estimate the risk of bites in travelers, and study the action they took before and after the incident. METHODS: Travelers presenting for pre-travel immunizations during the period of August through December 2004, who planned a travel of >or= 1 month's duration were retrospectively identified, contacted and interviewed by a structured questionnaire. These travelers did not receive specific advice concerning rabies. RESULTS: The study cohort comprised of 815 travelers (median age=25), of who 13 (1.6%) were injured by a potentially rabid animal (mainly, dog=6; monkey=4). The incidence of potential rabies exposure was found to be of 2.66 per 1000 travelers per month. Those injured had significantly longer trips than the non-injured (6.9+/-3.8 vs. 4+/-5.0 months, p=0.037); notably, the injuries occurred after a median of 5 weeks from departure. Although seven travelers noted blood at the site of injury, only four (31%) of the injured sought medical attention following the exposure, and all four received post-exposure prophylaxis. CONCLUSIONS: An injury by potentially rabid animals is not rare among long-term travelers. As the injury may occur early in the itinerary, rabies PEP should be considered for this population. Educational efforts are required in light of the lack of understanding of the dismal consequences of rabies among travelers.     

Rabies: relevance, prevention, and management in travel medicine

Rabies is a zoonotic viral disease, transmitted only in mammals. Terrestrial rabies, predominantly transmitted by dogs, is the most important rabies cycle threatening humans. The causative neurotropic virus is a negative-stranded RNA virus of the family Rhabdoviridae, genus Lyssavirus. This genus contains several rabies-related viruses. All variants are known or suspected to cause rabieslike diseases. Transmission occurs by the virus entering through the skin or the mucosa after bites, scratches, or preexisting injuries contaminated by the saliva of an infected mammal. Only 51 human rabies cases that have not been transmitted by animal bites are described.     

人用狂犬病疫苗和被动免疫制剂研发进展

狂犬病(Rabies)是由狂犬病毒(Rabies virus)引起的一种人兽共患病。人一旦发病致死率几乎100%。目前预防狂犬病的人用疫苗为狂犬病毒灭活疫苗。随着基因工程技术的进步,新一代以狂犬病毒G蛋白(Glycoprotein)为免疫原的疫苗在开发中,包括不同表达系统的G蛋白亚单位疫苗,G蛋白DNA疫苗,G蛋白病毒载体疫苗等。同时本文还探讨了未来可能取代狂犬病免疫球蛋白的被动免疫制剂(单克隆抗体)的研发进展。     

The epidemiology of animal bite injuries in Uganda and projections of the burden of rabies

OBJECTIVES: Rabies is a global problem, although it is often under-reported in developing countries. We aimed at describing the profile of patients presenting to health centres with animal bite injuries in Uganda, and use a predictive model to estimate the mortality of rabies at a national level. METHODS: We conducted a passive surveillance study in Uganda based in a random sample of health centres supplied with rabies vaccine to determine the characteristics of bite injury patients and establish the age and sex profiles of patients, the site of bites and their severity, wound management techniques and details of the vaccination course given. We also applied a decision tree model to the data to estimate the rabies mortality from the bite injury data using an established protocol. RESULTS: We found that most patients are bitten by dogs, and that a considerable proportion of these are young children, who are at greater risk of developing rabies in the absence of treatment due to the location of the bites they receive. From conservative parameter estimates, we estimate that in the absence of post-exposure prophylaxis (PET), 592 (95% CI 345-920) deaths would occur, and that if one dose of PET is sufficient for protection following a rabid animal bite, 20 (95% CI 5-50) deaths would occur annually. If a complete course of PET is required for protection following a rabid animal bite, up to 210 (95% CI 115-359) deaths would occur, as 41% of patients did not complete their course of PET. CONCLUSIONS: Active animal bite surveillance studies are required to improve our mortality estimates and determine the true burden of rabies in the Ugandan population. We emphasize the need for small-scale active case detection studies and improved data on the recognition of rabies in dogs as inputs for improving national-level estimates of rabies mortality.     

Knowledge, attitude and practices about animal bites and rabies in general community--a multi-centric study

Rabies a disease as old as our civilization, continues to be the most feared of all communicable diseases. Despite the availability the state-of-the-art tools which ensure near cent percent protection against rabies, India is the largest contributant to rabies mortality in the world. A multicentric study was carried out from April 2001 to September 2002 with the objective of assessing the knowledge, attitudes, beliefs and practices (KAP) about animal bites and rabies in the general community. The proforma for interviewing the general community was developed and used after field testing. The study was carried out at six selected centres across the country viz. Delhi, Hyderabad, Raipur, Jamnagar, Coonoor and Rajahmundry and was co-ordinated by National Institute of Communicable Diseases (NICD), Delhi, after thorough briefing of designated nodal officers. A total of 1129 (male: female :: 48.5: 51.5) persons in the age group of 18 to 80 years were interviewed in this study. Of these about 751% of the individuals had attended school at some level and rest were illiterates. 68.7% people had heard about rabies. In 60.7% of cases the community associates rabies with dog bite only. Knowledge about appropriate wound toilet was found to be inadequate. Only 360 (31.9%0/) people felt that washing the wound with soap and water was the best option. Application of indigenous products like chillies (11.4%), turmeric (5.6%), lime (6.8%), kerosene oil (2.3%), herbal paste (4.2%) etc was suggested along with visit to occult medicine practitioner (1.5%) as part of the bite wound management. People were not aware of number of injections needed for treatment of animal bites. Multiple reasons viz negligence and ignorance 354 (31.4%), fear of multiple painful injections 365 (32.3%), expensive treatment 169 (15%) and long course requiring daily visits to anti-rabies clinics 73 (6.5%) were cited as reasons for non-compliance of treatment. KAP study suggests that there is need to create awareness amongst the masses regarding epidemiology of the disease and merits of prompt and appropriate post exposure treatment through enhanced IEC activities.     

Gaps in the knowledge about advancements in rabies vaccines among the undergraduate medical students

Enormous developments have taken place during the past few years in the field of Rabies prevention and control particularly rabies vaccines. Intra-dermal Rabies Vaccination (IDRV) has already emerged as a safe, ethical and cost-effective replacement. However appropriate dissemination of knowledge and implementation by medical fraternity is imperative for effective prevention and control of this fatal disease. Gaps were found in the knowledge of medical students regarding the newer rabies vaccines. This can be resolved to great extent by updating the undergraduate curriculum with the current control strategies used in this field.     

Adverse Effects of Rabies Pre- and Postexposure Prophylaxis in 290 Health-Care-Workers Exposed to a Rabies Infected Organ Donor or Transplant Recipients

Abstract The recent unfortunate rabies transmissions through solid organ transplants of an infected donor in Germany required the initiation of a vaccination program to protect health care workers (HCWs) with close contact to rabies-infected patients. A systematic follow-up of adverse effects was initiated. Rabies postexposure prophylaxis (PEP) was started in 269 HCWs at four German hospitals. Pre-exposure prophylaxis (PreEP) was administered to 74 HCWs caring for an already diagnosed rabies patient. At each vaccination date, HCWs were interviewed for symptoms possibly representing adverse effects. Adverse effects of PEP and PrePEP were compared. Out of 269 HCWs, 216 were included for the investigation of adverse effects. Of these 216 HCWs, 114 (53%) individuals developed at least one systemic adverse effect. Incidences of tiredness (30.6%), malaise (26.4%), headache (26.9%), dizziness (14.8%), and chills (13.0%) declined in the course of PEP (p < 0.05), whereas incidences of fever (7.4%), paraesthesias (7.9%), arthralgias (1.9%), myalgias (4.2%), nausea (9.3%), diarrheas (2.8%) and vomiting (1.4%) did not. In 11 (5.1%) HCWs PEP was discontinued mostly due to adverse reactions (four suffered strong headaches, two HCWs meningeal irritations, two chills, one paraesthesia, one malaise, and one a rush). Systemic effects of PEP or PreEP did not differ significantly. Despite relatively high incidences of moderate severe adverse reactions rabies PEP is safe. Strong headache, tiredness, dizziness, and paraesthesias are the most important postvaccinal symptoms. Vaccinees suffering from adverse effects of PEP must be strongly encouraged to complete PEP, as it is to date the only protection against fatal rabies.     

Retrospective: animal attacks and rabies exposures in Thai children

Over 50% of animal bites and potential rabies exposures in Thailand are in children and they also have the more severe injuries due to inexperience, smaller size and less ability to fend off attacks. Potential rabies exposures and animal bites are common in Thailand. Majority of these are in children where the extent of the injuries is also much more severe. The bitten areas correlate to the age of the children and level of the bitten animal head. These are areas noted for a higher risk of infection with rabies virus and shorter incubation periods. The vast majority of bites are due to dogs (86%) of which 74.6% are stray or community-owned animals. The prevalence of dog bites shows no seasonal variation in adults but there are two peaks during school vacation period for children. Extensive educational efforts directed at the Thai public are responsible for the rapid presentation of victims for post-exposure treatment. The dramatic reduction of human rabies deaths in Thailand during the last decades was achieved largely by the provision of expensive WHO standard post-exposure treatment, utilizing modern tissue culture vaccines and immunoglobulins. Canine and feline rabies is nevertheless still endemic and not likely to be controlled or eliminated till sustainable humane methods of dog population control and comprehensive countrywide canine rabies vaccination become possible through government policy.     

Rabies in China: an update

Human rabies cases in China have continued to increase in recent years, reaching a new peak in 2007. Parallel with an increase in human rabies deaths, a number of animal species with rabies have been reported in the majority of rabies-endemic areas. In this report, the occurrence, status, and control of rabies in both humans and animals are reviewed. Vaccines and immunoglobulin for human and animal use and postexposure prophylaxis for human are also summarized. The current strategies for rabies elimination in China are presented.     

Evaluation of cases admitted to a center in Istanbul, Turkey in 2003 for rabies vaccination and three rabies cases followed up in the last 15 years

We evaluated the cases of 7,266 individuals who applied to our hospital's Center for Rabies Vaccination between January and December 2003. Among 1,831 female and 5,435 male cases, 37% were given 3 doses of vaccination, 14% were given 5 doses, and in 24% of cases a 2-1-1 vaccination schedule was applied. Antirabies serum of horse origin was given in 179 cases. Regarding the wounds, 83% were superficial and 17% were deep. Most of the cases involved dog bites (74%). Of the dogs involved, 30% were pets (with owners). Only a few (6%) of those pets had been vaccinated. Of the 2 dogs investigated for rabies in Pendik Veterinarian Research Institute, none were found to harbor the disease. In the last 15 years, 3 cases were followed up with a diagnosis of human rabies in our clinic. Domestic animals (without owners, living a somewhat wild life in cities) are still the cause of many rabies cases. As rabies carries a very high fatality risk, public health precautions and education are important as well as post-exposure prophylaxis.